Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects

  • Authors:
    • Yung-Yen Chiang
    • Shu-Li Wang
    • Cheng-Lin Yang
    • Hui-Yu Yang
    • Hsiu-Ching Yang
    • J. N. Sudhakar
    • Ching-Kuo Lee
    • Hsiu-Wen Huang
    • Chien-Min Chen
    • Shiow-Her Chiou
    • Shu-Fen Chiang
    • Hsin-Yuan Fang
    • Chih-Yi Chen
    • Shwn-Huey Shieh
    • Kuan-Chih Chow
  • View Affiliations

  • Published online on: July 12, 2013     https://doi.org/10.3892/ijmm.2013.1441
  • Pages: 577-584
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Abstract

Dihydrodiol dehydrogenase (DDH) is frequently detected in cancer cells, and its overexpression correlates with drug resistance, the downregulation of DNA repair mechanisms, increased frequency of tumor recurrence, cancer cell metastasis and poor prognosis. The silencing of DDH expression using siRNA, on the other hand, reduces drug resistance and cancer cell mobility. These data suggest that DDH may be an oncogene-related protein. However, no specific DDH inhibitor has been identified to date. Thus, in this study, we used DDH as a target enzyme in a live-cell enzyme-linked immunosorbent assay to screen Chinese medicinal herb extracts (CMHEs) with the aim of identifying a DDH inhibitor. Using this method, we found 49 among 796 CMHEs that inhibited DDH expression. We selected three potential extracts, which had the highest activity against DDH, for further fractionation using high-performance liquid chromatography. The active ingredient was identified by immunoblot analysis. The function of the active ingredient was characterized by cell function analysis. Our results revealed that the CMHE-purified compounds targeted DDH, inducing autophagy and reducing DNA repair, which in turn enhanced the cytotoxic effects of the anticancer drugs and irradiation.
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September 2013
Volume 32 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Chiang Y, Wang S, Yang C, Yang H, Yang H, Sudhakar JN, Lee C, Huang H, Chen C, Chiou S, Chiou S, et al: Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects. Int J Mol Med 32: 577-584, 2013
APA
Chiang, Y., Wang, S., Yang, C., Yang, H., Yang, H., Sudhakar, J.N. ... Chow, K. (2013). Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects. International Journal of Molecular Medicine, 32, 577-584. https://doi.org/10.3892/ijmm.2013.1441
MLA
Chiang, Y., Wang, S., Yang, C., Yang, H., Yang, H., Sudhakar, J. N., Lee, C., Huang, H., Chen, C., Chiou, S., Chiang, S., Fang, H., Chen, C., Shieh, S., Chow, K."Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects". International Journal of Molecular Medicine 32.3 (2013): 577-584.
Chicago
Chiang, Y., Wang, S., Yang, C., Yang, H., Yang, H., Sudhakar, J. N., Lee, C., Huang, H., Chen, C., Chiou, S., Chiang, S., Fang, H., Chen, C., Shieh, S., Chow, K."Extracts of Koelreuteria henryi Dummer induce apoptosis and autophagy by inhibiting dihydrodiol dehydrogenase, thus enhancing anticancer effects". International Journal of Molecular Medicine 32, no. 3 (2013): 577-584. https://doi.org/10.3892/ijmm.2013.1441